In studies on the function of substance P and on the effect of drugs on its distribution, the possibility that a pool of substance P precursor exists must be considered. The chick embryo dorsal root ganglion contains a molecular species of high molecular weight immunoreactivity which could function as a precursor in the formation of substance P. The content of this possible precursor is regulated by treatment of ganglia with nerve growth factor. Substance P, and its apparent precursor, have also been found in superior cervical ganglia, probably located in interneurons, as well as in many other tissues. Exposure of animals in utero to anti-NGF antiserum results in a loss of substance P from ganglia, spinal cord, skin, and ileum, a corresponding loss of somatostatin in spinal cord, ganglia and ileum, and no change in met5-enkephalin-arg6-phe7 in any of these tissues. Adults exposed to anti-NGF show comparable losses of substance P and somatostatin content without a change in cell number in the sensory ganglia, as well as a loss of substance P in adrenal medulla and ileum.